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Article

Combination of calcineurin B subunit (CnB) and 5‑fluorouracil reverses 5‑fluorouracil‑induced immunosuppressive effect and enhances the antitumor activity in hepatocellular carcinoma

  • Authors:
    • Wenlong Zhang
    • Youxiu Zhong
    • Hongfei Cui
    • Liya Wang
    • Rui Yang
    • Zhenyi Su
    • Benqiong Xiang
    • Qun Wei
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry and Molecular Biology, Gene Engineering and Biotechnology Beijing Key Laboratory, Beijing Normal University, Beijing 100875, P.R. China
  • Pages: 6135-6142
    |
    Published online on: September 15, 2017
       https://doi.org/10.3892/ol.2017.6958
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Abstract

Five‑fluorouracil (5‑FU) is a widely used chemotherapeutic agent for digestive system tumors; however, continuous use of 5‑FU may cause severe side effects, including myelosuppression and immunosuppression. Our previous study revealed that calcineurin B subunit (CnB), an innovative genetic engineering antitumor protein, possesses tumor‑suppressive effects with low toxicity. CnB can bind to and activate integrin αM on macrophages, subsequently promoting the expression, and secretion of TNF‑related apoptosis‑inducing ligand, a specific proapoptotic cytokine. In the present study, whether the combined use of CnB and 5‑FU can reverse the myelosuppression, and immunosuppressive effects of 5‑FU by reactivating the immune system thus increasing antitumor efficacy, was investigated. It was demonstrated that combined treatment of 5‑FU and CnB led to increased tumor‑suppressive effects, as indicated by reduced tumor volume and weight when compared with 5‑FU or CnB treatment alone in a hepatoma xenograph model. In addition, it was demonstrated that combined treatment inhibited the proliferation of hepatoma cells. Notably, the addition of CnB to 5‑FU‑based therapy completely reversed the immunosuppressive effect of 5‑FU. The spleen index and total number of white blood cells in the combination group were higher compared with that of the 5‑FU alone group. Furthermore, pathological examinations indicated that CnB attenuated 5‑FU‑induced organ damage. Based on these findings, it is proposed that CnB may serve as a novel and promising drug candidate for the improvement of 5‑FU‑based chemotherapy.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang W, Zhong Y, Cui H, Wang L, Yang R, Su Z, Xiang B and Wei Q: Combination of calcineurin B subunit (CnB) and 5‑fluorouracil reverses 5‑fluorouracil‑induced immunosuppressive effect and enhances the antitumor activity in hepatocellular carcinoma. Oncol Lett 14: 6135-6142, 2017.
APA
Zhang, W., Zhong, Y., Cui, H., Wang, L., Yang, R., Su, Z. ... Wei, Q. (2017). Combination of calcineurin B subunit (CnB) and 5‑fluorouracil reverses 5‑fluorouracil‑induced immunosuppressive effect and enhances the antitumor activity in hepatocellular carcinoma. Oncology Letters, 14, 6135-6142. https://doi.org/10.3892/ol.2017.6958
MLA
Zhang, W., Zhong, Y., Cui, H., Wang, L., Yang, R., Su, Z., Xiang, B., Wei, Q."Combination of calcineurin B subunit (CnB) and 5‑fluorouracil reverses 5‑fluorouracil‑induced immunosuppressive effect and enhances the antitumor activity in hepatocellular carcinoma". Oncology Letters 14.5 (2017): 6135-6142.
Chicago
Zhang, W., Zhong, Y., Cui, H., Wang, L., Yang, R., Su, Z., Xiang, B., Wei, Q."Combination of calcineurin B subunit (CnB) and 5‑fluorouracil reverses 5‑fluorouracil‑induced immunosuppressive effect and enhances the antitumor activity in hepatocellular carcinoma". Oncology Letters 14, no. 5 (2017): 6135-6142. https://doi.org/10.3892/ol.2017.6958
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang W, Zhong Y, Cui H, Wang L, Yang R, Su Z, Xiang B and Wei Q: Combination of calcineurin B subunit (CnB) and 5‑fluorouracil reverses 5‑fluorouracil‑induced immunosuppressive effect and enhances the antitumor activity in hepatocellular carcinoma. Oncol Lett 14: 6135-6142, 2017.
APA
Zhang, W., Zhong, Y., Cui, H., Wang, L., Yang, R., Su, Z. ... Wei, Q. (2017). Combination of calcineurin B subunit (CnB) and 5‑fluorouracil reverses 5‑fluorouracil‑induced immunosuppressive effect and enhances the antitumor activity in hepatocellular carcinoma. Oncology Letters, 14, 6135-6142. https://doi.org/10.3892/ol.2017.6958
MLA
Zhang, W., Zhong, Y., Cui, H., Wang, L., Yang, R., Su, Z., Xiang, B., Wei, Q."Combination of calcineurin B subunit (CnB) and 5‑fluorouracil reverses 5‑fluorouracil‑induced immunosuppressive effect and enhances the antitumor activity in hepatocellular carcinoma". Oncology Letters 14.5 (2017): 6135-6142.
Chicago
Zhang, W., Zhong, Y., Cui, H., Wang, L., Yang, R., Su, Z., Xiang, B., Wei, Q."Combination of calcineurin B subunit (CnB) and 5‑fluorouracil reverses 5‑fluorouracil‑induced immunosuppressive effect and enhances the antitumor activity in hepatocellular carcinoma". Oncology Letters 14, no. 5 (2017): 6135-6142. https://doi.org/10.3892/ol.2017.6958
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